Claudins 6, 9, and 13 are developmentally expressed renal tight junction proteins

Abstract

The adult proximal tubule is a low-resistance epithelium where there are high rates of both active transcellular and passive paracellular NaCl transport. We have previously demonstrated that the neonatal rabbit and rat proximal tubule have substantively different passive paracellular transport properties than the adult proximal tubule, which results in a maturational change in the paracellular passive flux of ions. Neonatal proximal tubules have a higher PNa/PCl ratio and lower chloride and bicarbonate permeabilities than adult proximal tubules. Claudins are a large family of proteins which are the gate keepers of the paracellular pathway, and claudin isoform expression determines the permeability characteristics of the paracellular pathway. Previous studies have shown that claudins 1, 2, 3, 4, 5, 7, 8, 10, 11, 12, 15, and 16 are expressed in the adult mouse kidney. To determine whether there are developmental claudin isoforms, we compared the claudin isoforms present in the neonatal and adult kidney using RT-PCR to detect mRNA of claudin isoforms. Claudin 6, claudin 9, and claudin 13 were either not expressed or barely detectable in the adult mouse kidney using traditional PCR, but were expressed in the neonatal mouse kidney. Using real-time RT-PCR, we were able to detect a low level of claudin 6 mRNA expression in the adult kidney compared with the neonate, but claudin 9 and claudin 13 were only detected in the neonatal kidney. There was the same maturational decrease in these claudin proteins with Western blot analysis. Immunohistochemistry showed high levels of expression of claudin 6 in neonatal proximal tubules, thick ascending limb, distal convoluted tubules, and collecting ducts in a paracellular distribution but there was no expression of claudin 6 in the adult kidney. Using real-time RT-PCR claudin 6 and 9 mRNA were present in 1-day-old proximal convoluted tubules and were virtually undetectable in proximal convoluted tubules from adults. Claudin 13 was not detectable in neonatal or adult proximal convoluted tubules. In summary, we have identified developmentally expressed claudin isoforms, claudin 6, claudin 9, and claudin 13. These paracellular proteins may play a role in the maturational changes in paracellular permeability.

The diagnostic and prognostic utility of claudin expression in renal cell neoplasms

“…36 Inversely, RON proto-oncogene product and S100 protein were found preferentially expressed in oncocytoma warranting further investigation. 37,38 Preclinical studies have demonstrated a developmental expression of claudin isoforms in the renal tissue, 39 and have identified a distinct pattern of expression of isoforms 7 and 8 along the mouse distal nephron. 10 Gene expression profiling studies in humans have proposed in recent years that chromophobe renal cell carcinoma and oncocytoma are distinguishable by mRNA expression profiles and have indicated claudin 7 as one of the candidate markers for chromophobe renal cell carcinoma.…”

Claudin-6, -10d, and -10e contribute to seawater acclimation in the euryhaline puffer fishTetraodon nigroviridis

“…This would indicate that cldn-6 may play a role in the physiology of the blood-brain barrier in fishes or other processes in the nervous tissue. In contrast, cldn-6 is absent from most adult mammalian tissues (including the brain) and its expression has been associated with prenatal developmental stages (Abuazza et al, 2006;Fujita et al, 2006;Morita et al, 1999;Morita et al, 2002;Reyes et al, 2002;Turksen and Troy, 2001;Turksen and Troy, 2002). Nevertheless, in adult mammalian tissues, Cldn-6 has been reported in the kidney (Morita et al, 1999;Zhao et al, 2008), taste buds (Michlig et al, 2007) and mammary gland (Quan and Lu, 2003), and in embryos and neonates, cldn-6 has been found in a variety of tissues that include the kidney (Zhao et al, 2008), the periderm of -ATPase (NKA; green) and (B) Cldn-6 (red) immunoreactivity show (C) colocalization of these proteins in ionocytes (arrowheads) with some peripheral punctate Cldn-6 staining around ionocytes (arrows).…”

Evolution of the vertebrate claudin gene family: insights from a basal vertebrate, the sea lamprey

“…Cldn 3 transcripts and protein were expressed in the developing mouse metanephric kidney, and overexpression of Cldn3 in in vitro model of kidney tubule formation promoted tubulogenesis (Haddad et al, 2011). Claudin 16 and Claudin 9 expression was observed in mouse embryonic and neonatal kidney (Abuazza et al, 2006, Khairallah et al, 2014. Additionally, Cldn16 knockout mice and humans with mutations in Cldn16 gene exhibit kidney disease (Gupta and Ryan, 2010).…”